Each protein has a unique amino acid sequence that defines its primary structure
Linking of amino acids in a linear polypeptide chain
α-carboxyl group of one amino acid is covalently linked to the α-amino group of another via peptide bond
The amino terminal end is the beginning of the polypeptide chain; carboxyl terminal end is the end of the polypeptide chain
Two amino acids linked together is called a dipeptide
Chain of more than two amino acids is called a polypeptide chain
All polypeptide chains are polar
Requires input of free energy (+21 kJ/mol) and loss of a water molecule to created a peptide bond
Requires +356 kJ/mol to break a peptide bond – very stable bond!
Molecular Weight
Molecular Weight (MW) is measured in Daltons which is equivalent to the atomic mass
Average MW of one amino acid is 110 Daltons
Most human proteins contain 50-2000 amino acid residues
MW would range between 5,500-220,000 Daltons
Polypeptide Chain
Polypeptide chain contains a peptide bond backbone and distinctive –R group side chains
Backbone always contains a carbonyl group, a good hydrogen bond receptor, an amine group (except for proline), and a good hydrogen bond donor
Backbone can interact with each other and with side chain functional groups
Disulfide bonds result in covalent cross-linking between and within proteins
-SH group forms disulfide bonds via oxidation
Two cysteine residues covalently bonded forms one cystine
Peptide Bonds
Peptide bond is essentially planar because of rigid double-bond-like characteristics
Peptide bond is uncharged, but is rich in hydrogen bond potential
For each pair of linked amino acids, there are 6 atoms within the same plane (amide plane)
Individual amino acids can be planar on their own individual amide plane
Planar peptide bonds can be in Trans or Cis configurations
Almost all peptide bonds are in Trans configuration because of steric hindrances in the Cis configuration
Amino acid linkages with proline causes steric hindrances in both configurations
Bonds in between peptide bonds have angles of rotation
phi (φ) is the angle of rotation between nitrogen of amino group and α-carbon
psi (ψ) is the angle of rotation between the α-carbon and the carbon atom of carbonyl group
Dihedral angle is the measure of rotation about each of the two single bonds – phi or psi
usually between -180° and +180°
Clockwise rotation is +
3/4 of possible phi and psi combinations are excluded sterically
Using Ramachandron diagrams, the precise protein folding can be predicted in large polypeptide chains
Secondary Structure
Secondary structure is the special arrangement of amino acid residues along the polypeptide sequence
Primary amino acid predicts secondary structure
Predictions based on rigidity of peptide bond and restricted set of allowed phi and psi angles
Two basic periodic (regularly repeating) secondary structures: α-helix and β-pleated sheets.
Secondary structure can be predicted to an extent with different probabilities of a certain amino acid forming part of an α-helix, β-sheet, or reverse turn.
α-Helix
α-Helix consist of a tightly coiled backbone with side chains extending outwards
Essentially all α-helixes in proteins are right-handed (clockwise) to reduce steric hindrance between –R groups and backbone
α-Helix is 1.5 Å wide with 3.6 residues per 360° turn
N-H group and C=O hydrogen bonds to stabilize secondary structure with bonds distributed 4 residues apart such that all backbone N-H and C=O groups are bonded
α-Helix are very strong and several helixes can super coil with each other to further enhance strength
β-Pleated Sheets
β-pleated sheets are more extended and looser in a zigzag structure
Adjacent amino acids are stretched 3.5 Å apart
Side chains are above and below the peptide bond
β-sheets are formed by linking two or more β-strands by hydrogen bonds
Can link parallel head to head (with amino terminal ends lined up) or anti-parallel head to tail (with amino terminal lined up with carbonyl terminal)
Parallel β-sheets hydrogen bond staggered between amino acids on opposite strand
Anti-parallel β-sheets hydrogen bond directly with amino acids on opposite strand
Amino acids can have both parallel and anti-parallel structure in the same protein
β-sheets can adopt a “flat and twisted” shape
Reverse Turns
Reverse turns that compact protein structures are not periodic but rigid
Often found on surface of protein and can interact between protein and other molecules
Most common structural element is the reverse turn (β-turn, hairpin loop)
C=O group of residue i hydrogen bonds with N-H group of residue i+3
Omega loops are more elaborate structures responsible for chain reversals
Introduction to Proteins II
Dr. Kandice Williams, Ph.D.
Table of Contents
Primary Structure
Molecular Weight
Polypeptide Chain
Peptide Bonds
Secondary Structure
α-Helix
β-Pleated Sheets
Reverse Turns
Objectives